PROJECT SUMMARY/ABSTRACT The Biospecimen Repository and Pathology Core is designed to provide support for the translational research efforts of the Genomic Instability in Breast Cancer SPORE, serving the SPORE RP1, RP2 and RP3, and developmental research projects. This Core will ensure a seamless integration of the current infrastructure available at Memorial Sloan Kettering Cancer Center (MSKCC), and constitute an essential component of this SPORE project, facilitating and expediting the collection, annotation, storage, distribution, and digital archiving and processing of biospecimens from breast cancer patients with specific patterns of DNA repair defects and/or genetic instability included in the SPORE research projects. This Core was also conceived to provide SPORE investigators with expert histopathologic evaluation of tumor samples from breast cancer patients enrolled in the research protocols, patient-derived xenografts and murine models described in this SPORE application, in conjunction with comparative pathologists from the MSKCC Laboratory of Comparative Pathology and the Genetically Engineered Mouse Phenotyping Service. The Core will also provide assistance in performing and interpreting immunohistochemical assays, in selecting tissue for microdissection and performing these microdissections, and in the generation of dedicated tissue microarrays. The Core will provide multiplexed immunophenotyping of the tumor and tumor microenvironment from breast cancers and breast cancer models. The specific aims of the Biospecimen Repository and Pathology Core include 1) to maintain and expand the systematic collection, annotation, and storage of bio-specimens for translational research of breast cancers with specific patterns of DNA repair defects and/or genomic instability, 2) to perform expert pathologic evaluation of all human breast cancer and animal models of breast cancer samples with specific patterns of DNA repair defects and/or genomic instability and preparation of appropriate material for use by SPORE investigators, and 3) to perform detailed immunophenotypic characterization of breast cancers and animal models of breast cancers with specific patterns of DNA repair defects and/or genomic instability. By centralizing and standardizing the pathology review of both human and murine breast cancer samples, from both clinical and research settings, and by working in conjunction with other Cores within MSKCC on the processing and curation of the biospecimen materials and digital images obtained from the samples included, the Biospecimen Repository and Pathology Core will help mitigate the impact of common confounders in translational research studies, as well as it will assist in the integration and prioritization of a variety of institutional pathology systems-related development efforts.